Linked Life Data

3474061

Source:http://linkedlifedata.com/resource/pubmed/id/3474061

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
14
pubmed:dateCreated
1987-8-20
pubmed:abstractText
DNA single-strand and double-strand breaks produced by doxorubicin and two anthracycline derivatives (4-demethoxy-daunorubicin and 4'-deoxy-4'-iododoxorubicin) were measured in doxorubicin-sensitive and -resistant P388 leukemia cell lines, using filter elution methods, and compared with cellular drug accumulation to account for major differences in their cytotoxic activities and cross-resistance. The increased cytotoxic potency of the two derivatives reflects at least in part the enhanced drug accumulation by cells that results from their increased lipophilicity. However, the level of protein-linked DNA breaks was not directly related to cellular accumulation of drug analogues. It is possible that enhanced cytotoxicity may also be the consequence of the greatly enhanced ability of analogues to cause DNA strand breaks. The resistant line showed only a modest degree of resistance to both anthracycline derivatives compared with the high degree of resistance to doxorubicin. Although for all the anthracyclines tested drug accumulation was reduced in the resistant line, this did not correlate with the degree of resistance. A differential sensitivity of resistant and parental cell lines to DNA cleavage activity was consistently found for all three drugs tested. However, in contrast to a lack of effect of doxorubicin, the derivatives caused appreciable DNA strand breakage in resistant cells. The enhanced ability of these analogues to break DNA in resistant cells is consistent with the slight cross-resistance with doxorubicin. DNA double-strand breaks produced in isolated nuclei from these cells paralleled the pattern found in whole cells, thus indicating that a nuclear alteration, presumably involving DNA topoisomerases, is associated with anthracycline resistance. Our findings strongly support the hypothesis that anthracycline resistance in these cell variants may be mediated by multiple mechanisms, involving alterations of plasma membrane and changes of nuclear enzymatic activities responsible for DNA strand breaks.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
0008-5472
pubmed:author
pubmed:issnType
Print
pubmed:day
15
pubmed:volume
47
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
3752-6
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
1987
pubmed:articleTitle
Markedly reduced levels of anthracycline-induced DNA strand breaks in resistant P388 leukemia cells and isolated nuclei.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't